{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:26:23Z","timestamp":1770143183605,"version":"3.49.0"},"reference-count":139,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>Disease epidemiology during the COVID-19 pandemic differed greatly across the globe. In contrast to early pandemic predictions, Africa recorded the fewest SARS-CoV-2 related hospitalizations and deaths. Hypotheses proposed to explain this paradox include underreporting, age demographics, climate, national mitigation strategies, lifestyle factors, pre-existing cross-reactive protection, and host genetic determinants. This traditional, narrative review evaluates these hypotheses investigated in the published literature, and highlights knowledge gaps which limit our understanding and obscure validation of potential explanations. It also discusses how responses to vaccines, the primary intervention sought to control infectious disease outbreaks, may vary both within the African population and across other continents. Potential explanations in the literature include pre-existing immunity, poor nutrition, immune modulating co-infections, comorbidities, microbiome composition, genetic polymorphisms, and demographic factors. Previous studies have shown that pre-existing (infection-derived) immunity or cross-reactive immune responses can augment vaccine-elicited positive responses and can protect against reinfection in a way similar to immunization. Conversely, there are also studies showing that prior immunity interferes with the efficacy of new vaccines through mechanisms like original antigenic sin and immune imprinting. Thus, there is need for more immunology studies to understand the relative contribution of pre-existing cross-reactive immune responses to the epidemiology of new pathogens. These studies are particularly essential to understand the differences between pandemic preparedness and population vulnerability, as well as to inform vaccine development and vaccine effectiveness monitoring studies. SARS-CoV-2 serves as an important case study to understand heterogeneity between and within populations in immune responses to both the pathogen and to vaccination. This understanding is crucial in informing vaccine research and development aimed at supporting the 100-day mission for when the next pandemic threat emerges.<\/jats:p>","DOI":"10.3389\/fpubh.2026.1761547","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:30:04Z","timestamp":1770100204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A narrative review of heterogeneity in SARS-CoV-2 infection outcomes and vaccine efficacy: strategizing pandemic preparedness in Africa"],"prefix":"10.3389","volume":"14","author":[{"given":"Trisha","family":"Kerai","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, Ashworth Laboratories, King\u2019s Buildings, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Tackling Infections to Benefit Africa (TIBA) Partnership, TIBA Global Health Research Unit, Ashworth Laboratories, King\u2019s Buildings, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Woolhouse","sequence":"additional","affiliation":[{"name":"Tackling Infections to Benefit Africa (TIBA) Partnership, TIBA Global Health Research Unit, Ashworth Laboratories, King\u2019s Buildings, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Usher Institute, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman Z.","family":"Nyazema","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Pharmacology, National University of Science and Technology","place":["Bulawayo, Zimbabwe"]},{"name":"Department of Pharmacy, University of Limpopo","place":["Sovenga, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Mutapi","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, Ashworth Laboratories, King\u2019s Buildings, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Tackling Infections to Benefit Africa (TIBA) Partnership, TIBA Global Health Research Unit, Ashworth Laboratories, King\u2019s Buildings, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"100736","DOI":"10.1016\/j.jbior.2020.100736","article-title":"SARS-CoV-2 pandemic: an overview","volume":"77","author":"Acuti Martellucci","year":"2020","journal-title":"Adv Biol Regul"},{"key":"ref2","volume-title":"COVID-19 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